Two groups of deletion mutants of the alpha platelet-derived growth factor receptor (PDGFR) have been generated to further investigate the structural requirements of the alphaPDGFR for binding PDGF-AA and a monoclonal antibody (mab) against alphaPDGFR designated mab alphaR1. The mab alphaR1 was recently reported to block high affinity binding of PDGF- AA to alpha PDGFR. The first group of mutants were carboxy terminal deletion mutants encoding the first two immunoglobulin (Ig)-like domains. alphaR1-216; the first four Ig-like domains. alphaR1-415; or all five Ig- like domains. alphaR1-530. of the alphaPDGFR. Using conditioned medium from NIH/3T3 transfectants. mab alphaR1 was able to immunoprecipitate each of the secreted forms of alphaPDGFRs suggesting that the epitope recognized by mab alphaR1 is located within Ig-like domains 1 and 2 of the alphaPDGFR. Furthermore. PDGF-AA exhibited detectable binding to alphaR1-415 or alphaR1-530. but failed to interact with alphaR1-216. suggesting that the first two Ig-like domains of the alphaPDGFR are not sufficient for PDGF-AA binding. The second group of alphaPDGFR mutants were internal deletion mutants lacking Ig-like loop 1 (alpha-R-delta-49- 100). Iglike loop 2 (alpha-R-delta-150-189). Ig-like loop 3 (alpha-R- delta-235-290) or part of Ig-like loops 4 and 5 (alpha-R-delta-375-450). The internal deletion mutants were transfected into 32D cells which lack both band 13 PDGFRs. PDGF-AA bound with high affinity to 32D cells expressing (alpha-R-delta-375-450 but not to 32D cells expressing the other three internal deletion mutants. In addition, mab alphaR1 could immunoprecipitate alpha-R-delta-49-100. but not alpha-R-delta-150-189 in cell lysates of the 32D transfectants. Together these results suggest that major high affinity epitopes for PDGF-AA binding are located within the first three Ig-like domains and that mab alphaR1 is located within Ig-like domain 2 of the alphaPDGFR.